POS1009 RADIOGRAPHIC AIRWAY ABNORMALITIES IN UNTREATED EARLY RHEUMATOID ARTHRITIS ARE ASSOCIATED WITH PERIPHERAL NEUTROPHIL ACTIVATION
Authors: C. Kärrman Mårdh, T. Selldén, M. Joelsson, J. Vikgren, Å. Johnsson, G. Larsson, D. Glinatsi, K. Stubendorff, K. Svensson, I. Gjertsson, A. Rudin, A. C. Lundell, A. K. H. Ekwall
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear [1]. Up to 10% of RA patients develop severe treatment resistant lung disease [2]. Understanding early disease mechanisms is of great importance. Neutrophils are key players in RA pathogenesis and are recruited to the lungs early in the disease [3]. In RA, circulating neutrophils display an activated phenotype and neutrophil activation markers predict joint destruction and development of extra-articular nodules [4]. Neutrophil activation status has not been studied in relation to pulmonary abnormalities (PA) in early untreated RA (ueRA). <h3>Objectives</h3> To determine whether there is an association between peripheral neutrophil phenotypes and presence of PA on chest high-resolution computed tomography (HRCT) in ueRA. <h3>Methods</h3> Clinical data and blood were collected, and HRCT performed at diagnosis on 30 consecutive anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) positive ueRA patients. HRCTs were evaluated for the presence and extent of RA-associated parenchymal, airway and/or pleural abnormalities. Expression of phenotype markers on neutrophils separated by density was determined by flow cytometry. Levels of calprotectin, ACPA and RF were measured using immunoassays. An initial principal component analysis was used to visualize the relationships of the multidimensional data followed by univariate analysis of the strongest associations. <h3>Results</h3> The median patient-reported symptom duration was 6 months, 20 % of the patients were current smokers and the mean disease activity was moderate in this seropositive ueRA cohort. The frequency of having any PA detected by HRCT was 60 %. Airway abnormalities were present in 50%, nodules in 43 % and interstitial lung abnormalities (ILA) in 10 %. Unsupervised multivariate factor analysis showed clustering of "any PA" with neutrophil activation, parameters of inflammation and RF titres (Figure 1A). Univariate analysis confirmed a significantly increased CD11b and decreased CD62L expression on neutrophils indicating activation in patients with PA as compared to no PA. Titres of RF, but not ACPA, correlated with expression of the neutrophil activation marker CD11b. A stratified analysis demonstrated that airway involvement was the PA subtype with the strongest association with neutrophil activation (CD11b 1.3-fold, p=0.014 and CD62L 0.6-fold, p=0.003 in patients with airway abnormalities as compared to no PA) and with RF IgM titres (8.8-fold, p=0.0002) (Figure B-E). <h3>Conclusion</h3> We report a significant association between radiographic airway findings and activation of circulating neutrophils in early RA supporting a role of innate immunity and the lung in disease onset. Our results also indicate different contributions of RF and ACPA in the RA pathogenesis. Parts of this abstract was presented 15 September 2022 on a national rheumatology meeting in Gothenburg, Sweden. <h3>References</h3> [1] Reynisdottir et al. Arthritis Rheumatol, 2014 [2] Wang et al. Nat Rev Rheumatol, 2019 [3] Demoruelle et al. Arthritis Rheumatol, 2017 [4] Bach et al. Arthritis Rheumatol, 2020 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.